Bratus-Neuenschwander Anna, Castro-Giner Francesc, Frank-Bertoncelj Mojca, Aluri Sirisha, Fucentese Sandro F, Schlapbach Ralph, Sprott Haiko
Functional Genomics Center Zurich, University of Zurich/ETH Zurich, 8057 Zurich, Switzerland.
Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich/University of Zurich, BioTechno Park Schlieren, 8952 Schlieren, Switzerland.
Genes (Basel). 2018 Jul 4;9(7):338. doi: 10.3390/genes9070338.
Joint pain causes significant morbidity in osteoarthritis (OA). The aetiology of joint pain in OA is not well understood. The synovial membrane as an innervated joint structure represents a potential source of peripheral pain in OA. Here we analyse, using a hypothesis-free next generation RNA sequencing, the differences in protein-coding and non-coding transcriptomes in knee synovial tissues from OA patients with high knee pain ( = 5) compared with OA patients with low knee pain ( = 5), as evaluated by visual analogue scale (VAS). We conduct Gene Ontology and pathway analyses on differentially expressed mRNA genes. We identify new protein-coding, long non-coding RNA and microRNA candidates that can be associated with OA joint pain. Top enriched genes in painful OA knees encode neuronal proteins that are known to promote neuronal survival under cellular stress or participate in calcium-dependent synaptic exocytosis and modulation of GABA(γ-aminobutyric acid)ergic activity. Our study uncovers transcriptome changes associated with pain in synovial microenvironment of OA knees. This sets a firm ground for future mechanistic studies and drug discovery to alleviate joint pain in OA.
关节疼痛在骨关节炎(OA)中会导致严重的发病情况。OA中关节疼痛的病因尚未完全明确。滑膜作为一种有神经支配的关节结构,是OA外周疼痛的一个潜在来源。在此,我们使用无假设的新一代RNA测序技术,分析了根据视觉模拟评分法(VAS)评估的膝关节疼痛程度高的OA患者(n = 5)与膝关节疼痛程度低的OA患者(n = 5)的膝关节滑膜组织中蛋白质编码转录组和非编码转录组的差异。我们对差异表达的mRNA基因进行了基因本体论和通路分析。我们鉴定出了可能与OA关节疼痛相关的新的蛋白质编码、长链非编码RNA和微小RNA候选物。疼痛的OA膝关节中富集程度最高的基因编码的神经元蛋白,已知其在细胞应激下可促进神经元存活,或参与钙依赖性突触胞吐作用以及γ-氨基丁酸(GABA)能活性的调节。我们的研究揭示了与OA膝关节滑膜微环境中疼痛相关的转录组变化。这为未来缓解OA关节疼痛的机制研究和药物发现奠定了坚实基础。